Internaf Newsletter April 2000 Issue Page 4 Home    Index    Page1    Page2    Page3    Page4 SENT TO YOU FROM FARA- the Friedreichís Ataxia Research Alliance  Idebenone Clinical Trial - Substantive Update Will Idebenone be a wonder drug? Will Idebenone - alone or in a cocktail with other anti-oxidantsóslow the progression of Friedreichís ataxia (FRDA)? Will other anti-oxidants that are cheaper and more easily obtainable prove to be just as effective as Ibebenone? Will Idebenone reach orphan drug status? How long will it take? How much will it cost? The list goes on and on. These are the questions for which patients and their families want answers quickly. Is Idebenone safe, by U.S. legal standards, for use by children and adults with FRDA? What methods are to be used to determine if Idebenone is effective? Is it more effective than other drugs? What combination of such drugs is most effective? Should all patients in such a clinical trial be assured of receiving at least a ìstandard of careî amount of antioxidants while it is being determined whether adding Idebenone makes a difference?  Who will develop the scales of measurement so that the patientsí progress can be measured accurately? How do we ensure that the scales are applied with complete consistency from center to center? Can FDA approval be streamlined? Can the Orphan Drug Act be employed? Ensuring safety, measuring improvement accurately, identifying the most effective treatment and dosage for that treatmentóall as quickly as possible, to U.S. FDA standards, and at a reasonable costóthese are the technical challenges the research community must address. This memo addresses the purpose of an Idebenone Clinical Trial; the FDA & the Orphan Drug Act; and, Phase I of this effort - the pilot trials. The pilot trials will involve a small number of patients.  Phase II - the full-scale, multi-center, international clinical trialówill require hundreds of patient volunteers. FARA will refine the patient database to prepare for each phase. What are the Purposes of an Idebenone Clinical trial centered in the United States? 1.  To test the safety and efficacy of Idebenone in the treatment of FRDA symptoms (for example, hypertrophic cardiomyopathy and ataxia - loss of muscle strength and coordination). 2.  To obtain Food and Drug Administration (FDA) certification of Idebenone as a compound useful in the treatment of symptoms of FRDA.  How might the Orphan Drug Act be involved? Because of reduced profit potential, the normal drug sponsors are reluctant to invest the time and money necessary to develop treatments in a limited market such as patients with a rare disease. Other potential sponsors, such as research hospitals and universities, often lack the capital and business expertise to develop treatments for limited patient groups. To address this disparity, Congress enacted the Orphan Drug Act, which grants special privileges and marketing incentives to drug sponsors that help develop pharmaceutical treatments for rare diseases. The Orphan Drug Act defines orphan products as ones used to treat diseases or conditions affecting fewer than 200,000 patients in the United States. Of course, there are far fewer than 200,00 FRDA patients in the country. Typically, FDA approves orphan products much more quickly than products aimed at potentially huge markets. Nonetheless, some in the orphan diseases community say FDA approval still takes too long. The agency may aim to speed approvals, but it wonít take shortcuts. The bottom line is that the American public will not forgive FDA if a potentially harmful drug is approved and sent out. For further information on this issue, see http://www.fda.gov/fdac/special/newdrug/orphan.html For extensive information on the guidelines that must be followed to apply for orphan drug status, visit http://www.fda.gov/orphan/about/odreg.htm (Food and Drug Administration Regulations regarding the Orphan Drug Act) Why is it important to secure FDA approval of FRDA treatments? Currently, Idebenone is available over the internet through International Anti-aging Sytems (IAS) at http://www.antiaging-systems.com With a daily dosage of 5 mg/kg of body weight, a supply via this internet source for a patient weighing 120 pounds would  be approximately $240 per month/$2880 per year. FDA approval of Idebenone, for example, would allow a patientís doctor to write a prescription for this compound for the treatment of FRDA. The cost of the drug would be greatly reduced based on the patientís prescription coverage under his or her private health insurance company, Medicaid or Medicare. To secure FDA approval of Idebenone, specific technical objectives must be met during Phase I and Phase II of the Idebenone trial. Phase I. 3 pilot trials must be successfully completed prior to the implementation of a full-scale clinical trial: 1. Ataxia Scales: The first pilot trialTools of measurement to identify progress or lack of progress in symptoms related to FRDA. Currently, there is no internationally verifiable and accepted method of measuring progress or lack of progresss in FRDA symptoms. Scales will be developed that can be used consistently at different centers worldwide with a predictable degree of accuracy.  Interrater reliability: Once a standardized set of ataxia scales is developed, the researchers must also develop guidelines and training so that health professionals rating each patientís performance will be objective and consistent. 2. Pharmacological study in children: Even though Dr. Rustinís trial in France shows very promising results with Idebenone in children, there is no data available from any FDA- certified trial on the safety of using Idebenone in children. Therefore, a small number of children (probably ages 6-16) with FRDA will participate in an NIH-based pilot trial to establish definitively that the drug is safe in kids. Idebenone use in adults: Idebenone has been used in FDA-certified trials for adult-onset diseases such as Alzheimerís disease and Huntingtonís disease.  Data from these trials can be used for safety determination, so no pharmacological study is necessary in adults. 3. Toxicology studies in animals: This study should take about a month to complete and will be done on rats. NIH will contract out the study. No problems are anticipated. All three pilot trials can be done simultaneously. Patients for the ataxia scales trial and the pharmacological study with children will be recruited from the Washington, D.C. metropolitan area and outlying region in order to limit the costs of the trials and maximize the convenience for patients. The FARA patient database will be a key source of potential patients who have expressed interest in participating in the trials. Even as these preparations for the three pilot trials are underway, preparation has already begun of the grant proposal for the full scale, multi-center trial (Phase II) testing the efficacy of Idebenone. That proposal will be submitted to the National Institutes of Health (NIH) for funding. We know the answer to one question we all have - will this take longer than ìIî would like?. YES! Researchers are hard at work NOW with the technical, logistical, legal and ethical considerations that must be addressed before the pilot trials and the full-scale trial can begin and the FRDA patients can participate. We share your sense of urgency because we have a 14 year old son with FRDA also. We, too, wonder how long it will take to find a treatment or cure.  Will it be ìin timeî? In time for what? - A longer life, slower progression, living with fewer symptoms? Together weíre moving the mountainóstone by stone. We are thankful for the brilliant research community hard at work every day at the nationís leading research facility, NIH, and at universities, hospitals and medical clinics around the world. Collaboration between these fine minds, along with the support of patients, patient families, FARA, NAF and MDA will accelerate this process. FARA will continue to keep you updated as further information becomes available. Together we CAN and WILL make a difference. Sincerely, Ron Bartek FARA President   Sent to you from FARA - the Friedreichís Ataxia Research Alliance Gene Map Milestone Celera Genomics Group of Rockville said yesterday that it has completed several months ahead of schedule the first key phase in decoding the human gene code... The company said it has completed decoding the chemical sequences of DNA that determine each personís makeup, directing cells on every range of characteristic, from eye color to susceptibility to certain diseases.  The next step, which the company says it will complete within weeks, is to arrange these chemical sequences in the order they appear in relation to each other in the cells of humans. Industry executives and analysts liken the achievement announced yesterday to that of defining every piece in a jigsaw puzzle. The next step will be to put the pieces together. Celera is racing against a federal government effort to be the first to decipher the complete biological blueprint of the more than 3 billion pairs of chemicals that make up human DNA. The DNA is arranged in specific relationships to create an estimated 80,000 to 120,000 human genes, which run every process in the body. Scientists believe that detailed knowledge of the human genome will open the door to developing breakthrough drugs and other therapies to treat many diseases. ìBut itís important to point out that the final, highly accurate, completed sequence of the human genome by any group is probably a couple of years away,î NIH/NHGRI Director Francis Collins said. He said the public effort, whose work is posted daily on the Internet, ìhas made it possible for Celera to reduce by more than half the amount of work it originally expected to have to do.î ìIt would be a huge mistake to say that this company has sequenced a human genome,î said Eric Lander, director of the Whitehead Center for Genome Research in Boston, which estimates it has contributed about 25 percent of the publicly available sequenced information so far. ìPeople may have the misimpression that a private company has sequenced the human genome. Today more than 70 percent of the human sequence is already on the Web from the public sequencing project. Weíre proud of that and weíre glad Venter has been able to use that data to help him get to where he is.î Complete article: http://www.washingtonpost.com/wp-dyn/articles/A27071-2000Apr6.html Washington Post Friday, April 7, 2000; Page E01    2000 Annual Membership Meeting - Biloxi, Mississippi  Program for Parents with Ataxians, March 24, 2000 Meeting Notes: Action Items: •       Valerie Bennett will e-mail out information on van conversion companies - approved by Ford & GM & approved by the U.S. Govít for crash tests * Marilyn Downing & Mary Bode to work on summarizing educational issues - high-level suggestions, key references, what to do, etc.  Key Take Aways: •       Attendance  ~70  Financials (Facilitator:  Paul Konanz)  Paul welcomed everyone to the family of parents of kids with ataxians.  This is the first year of a pilot to get group inputs, a discussion group. Agenda: •       Greeting/Introductions •       Parental Financial Planning •       self-sufficiency •       Group Discussion •       Q&A  Suggestions for the day •       Emphasize helping the new parents •       Be mindful of the large group - short, brief sharing •       Ask & Share - the group has the knowledge •       Agendas will change - dyanmic & group-driven •       Post-program suggestions - Fri, 8:30 PM •       Traditional parents meeting - Sat, 4:30 PM   New parent introductions - 12-ish new families, diagnosis in the past 3-9 months, typically 11-14 of age for diagnosis Parental Financial Planning - ArnieGruetzmacher  For the past 15 years, Arnie has been exclusively focused on clients with disability. Need to plan ìWhat happens IF?î - if the worse case scenario happens.  What if something happens to me, the parent?  Best method is a Supplemental Needs Trust. Supplemental Needs Trust is part of your will.  You first exclude them from your estate.  Next establish a Supplemental Needs Trust, with X amount designated to the disable child.  It is a separate entity in your will/family.  Itís ran by the trustee, with successor trustees (family members or third parties).  All governmental assistance continues after parents pass away.  This provides for needs, over and above what the government provides. The other thing should be to set up a Durable Power of Attorney for the parents - give someone else the authority to sign your name for financial reasons.  Also, write a Letter of Intent.  An LOI defines the parentsí hopes, desires & dreams regarding your child with a disability, to assure their quality of life continues.  This will provide guidance to your successors. Keep documents readily accessible.  Review them every 3 years.  Tell your successors/children what youíre planning, so theyíre not surprised.  Arnieís phone # -- high-level questions or to talk with your local financial professional - 800 487-5310 Ticket to Work/Self-Sufficiency Law - Ron Bartek (Work Incentives Improvement Act of 1999) New, recent legislation currently is being developed in the House of Representatives & Senate.  Provides incentive to those with disabilities to be able to work.  This law has not yet been implemented.  Guidelines & regulations are still being developed. 1. Disabled American - needs training & vocational services.  If  I get a job I lose medical coverage & insurance.  This law extends medical coverage. 2. Employer - A ìTicket to Workî goes to the local Vocational Service Provider, the vocational service provider gets rewarded if the disabled person finds a job.  The ticket can be taken to any employer (public or private).  There are incentives for employers to hire.  Call or e-mail your local representative is.  Go to the NAF web page for contact information.  Also, go to your local Center for Independent Living.  Independent Living Centers - non-governmental, non-profit centers that care about helping people with disabilities live independently - information on: housing, governmental regulations, Social Security.  Santa Rosa Californiaís Independent Living Centerís phone # -- 707 528-2745 - they can give you the phone number of all the centers in your state (some info may be old). Financing Assistive Technologies  Converting Vans - with new vans, there are conversion packages - possibly limited to ~$1k.  Suggestion to talk with a van conversion company BEFORE buying the van, to assure which vans can be converted, and which ones are the easiest.  Many of the conversion companies will only do new vans.  There are basically 4 companies (approved & warranted by Ford & GM, approved by US Govít) that do conversions - go to the dealers of the conversions.  Look under ìwheelchairsî in the yellow pages.  US Disabled Vans - there are a number of companies, esp. in Arizona.   Most easily converted - Dodge Caravan & Ford Winstar. Financing Van ConversionsóHow do you pay for the additional $8k for conversion?  There are ADA loans available.  Again, check with the Independent Living Center for information on conversion assistance options - they are a great resource of information. Vocational Rehab - often linked to a child being ìindependentî, age 18 and formally declared as financially-independent of the parents. Government intent is to assist the individual to get a job through education. Hand controls for cars/vans - may be covered by assistive programs, fits on many vehicles. MDA can be a good funding source - esp. for wheelchairs.  Children have a $1,700/3yrs. account with MDA, for ages under 18 or 20.  Focused on wheelchairs & braces & their maintenance.  Also Shriners (equipment & surgery). Ataxians & Driving States and some hospitals can provide evaluation on when should an ataxian stop driving, but it is really a matter of the ataxianís judgement (independence, remember?). For learning to drive, even if a professional teacher says they donít have the ability, use the beginnerís permit to let your ataxian experience driving so they can always say they did it. Financing for Wheelchair Chair Lifts on Vans Q:  If your insurance company declines coverage, can the cost be tax deductible?   A:  It may be, it has been for house remodeling.  See a tax expert - varies from state to state.  Keep receipts - broadening doors, new door knobs, bars, etc. Home Modifications Check with local governmental agencies to find out about funding, grant money, down payments.  There are often lots of programs.   Another funding source my be a fund-raising agency, e.g., the Elks. Financial Thoughts (Information from informal discussion at an Independent Living Center - again, they ARE a resource for information) •       Cash is not traceable •       Must notify all support systems of changes •       Must understand the social support systems •       In any meeting look your worst not your best - show them ìrealityî •       YOU must ask, ìtheyî donít just give •       Keep copies - for 10 years! •       Change of workers can change rules •       SSI over payments •       Always put in the waiver request •       SSI goal is repayment in 3 years •       Reason for waiver •       Not my fault with reasons •       Canít pay •       If the parent dies, retires, or goes on SSDI, SSI automatically starts the process to move the FAíer to the parentís SSDI account •       Look carefully at the pros/cons of SSI vs. SSDI - for you and your FAíer •       If FAíer doesnít want SSDI just donít prove medical before 22 disability (a reverse negative - donít prove disability to stay in SSI) •       Uncovered medical •       Doctor samples •       Doctor/you write to manufacturer for free medication  Care Giver Mental Health (Facilitators:  Thom Fritz & LaVerne Hawthorne) Relationships Thom Fritz - we need to be willing to start from accepting them, the way they are.  Let them make mistakes and let them pay for their mistakes - ìown their consequencesî.  How do you prevent co-dependency or a desire to ìcontrolî your FA child?  (E.g., taking CoQ10)    We need to remember that our FA children are desperate for taking some type of control. It helps to share whatís motivating our behaviors and concerns, and then to ask our FA children why theyíre behaving the way they are, or why they have specific concerns - i.e., ìwhatís your motivation?, hereís mineî.  Open-ended listening. Talking about FA Ideas --> bring Support Group meetings to your home.  Go ahead and talk to them, even if they wonít listen to you. We donít know what our FA kids go through throughout the day.  What are their challenges? The guilt the parent feels.  Isolation and how we deal with this.  Isolation can lead to depression. Let other kids know what is going on with FA child.  What people say can be hurtful. Things people say are sometimes are not comforting.  Other people sometimes like understanding what is going on with affected child.  Others can move on.  Our grief continues.  Isolation from friends.  They can move on, but we continue to face our struggles on a day to day basis. Some deal best with isolation.  We as parents have to fight. We all are given one life and we have to learn to deal with our issues. Acceptance.  Parents need a balance between talking about issues openly.  Our children need this same balance.   ìMuch harder on the parents than the child.î  Professional counseling can be very very important.  For both parents and the children.  Counseling can help the FA person realize that they are a person, no matter their limitations.  If the child has problems of isolation, depression, worthlessness, it is definitely worth it to get counseling. Depression.  Metabolic balance is different amongst FAíers which can be a cause of their depression.  RELATIONSHIPS:  Get relatives to treat the affected child the same as other children in the family.  Try to tell your family to treat everyone equally.  Demand the same respect.  Dealing with extended family can be difficult.  Within the family (especially the parents), there has to be unity.  Extended families can, as well, receive counseling.  CAREGIVERS: As caregivers, how healthy are we?  Are we taking care of ourselves?  Do we as caregivers have our own interests?  It is really really important that we stay physically and emotionally healthy as parents.  If we are not healthy, we too become the victims.  Couples split up because of disabilities.  Couples must take care of themselves.  Schedule a time for yourself in your planner.  Attend a caregivers training session!  One to two hour courses on how to be a caregiver and how to get away.  In-Home Support Services provides caregiver training.  They can offer suggestions and guidance. GET EDUCATED on the avoidance of burnout.  Burnout is real - slow and insidious.  National Family Caregivers Association nhall@ap.net <mailto:nhall@ap.net>  - caregivers.org. There are respite organizations, State In-home support Services, Disorder Organizations. A lot of states will pay some amount for caregivers. Teaching our children to be independent.  How to shop, cook and clean.  We need to teach our kids how to live independently after they become independent.  TAB - Temporarily able bodied. FAíers:  Various  Topics. Acceptance- •       How do we help our older teenager deal with the anger he feels?    One older Faer suggests letting them be angry.   Parents need to separate themselves from their childrensí anger.  ìPaxilî, an antidepressant, is effective for some. A new parent expressed concern about bringing her son to these meetings.  The overwhelming consensus was that our children benefit a great deal from coming to these meetings.  School- Marilyn and Mary provided information on dealing with the schools.  Marilyn provided a list of modifications/accommodations, and they stressed the need to push for physical and occupational therapy provided by the school if you want it.  Sharon indicated that many parents have had difficulty getting the school to provided needed services. Paul stressed the need to know about ìSection 504î, a law which strengthens parentsí rights, a copy of which you can get from your school district.   ìIDEAî Individuals with Disabilities Education Act, covers IEPs.  We discussed the importance of informing our childrensí peers about FA.  Ron Bartek FARA - NIH asked for a patient-advocacy group for FA.  The mission of FARA is to support research on FA.  NIH budget is being doubled by 2003.  FARAís working with Congress & NIH.  May 20th, 2000 may be declared National FA day!  Last Oct was the first 3-day FA workshop at NIH - $48k of funding (idebenon, sticky DNA, mouse models, iron kelations). Idebenone - NIH is working on an FDA-approved Idebenon trial.  Pilot trials planned at the end-of-May.   This trial will cover combinations of NAC, CoQ10 & E with Idebenon.   Dr. Susan Perlman Medical Q&Aís Q:  FAíer wakes with ìkillerî headaches, nausea, throws up, etc..  What can be done?  Age 11 A:  There are a lot of FA-related complaints - leg, blader, etc.   In her practice thereís only been one other patient with headaches & vomiting problem.  Make sure nothing else is going on. Q:  When might we see a cure &/or treatment? A:  Research is going very quickly.  Optimistic researcher often talk of getting curative treatments in the 5 year timeframe, but see Dr. Pandalfo for details on FA - he knows more and can see further out.  Q:  Hard to get to sleep w/FA?  Is this typical? A:  Not everything is necessarily associated w/FA - could, however, be restless legs, breathing problems, etc.   Mostly caused by some type of discomfort.  FA is mostly a fatiguing illness  Q:  Is there a problem with anesthesia & FA? A:  Maybe a concern with the heart & the stress on the heart, especially with cardio-myopothy.  Also, there may be a longer recovery time & longer rcuperation time - longer to bounce back.  Q:  During a womanís menstration, are there increased problems with FA. A:  Yes, there seems to be some indication in increased systems.   Q:  Problems walking (extremely tender legs/feet) especially with the flu or viral illness. A:  Some muscle aches might be felt more intensely if you have FA, when you have a muscle-related illness.  Q:  Use of herbs w/QoC10, NAC, E - calcium, magnesium, ...? A:  Herbal & vitamin remedies may interact with prescriptions - always check with pharmacist & on-line references.  Also, start one thing at a time.  Q:  Immune systems problems w/FA? A:  None seen in any studies.  Q:  Medications w/cardiomyopathy? A:  Tylenol is OK, infrequently.  Cough syrups - check with your doctor. Tylenolís effect may get negated by NAC (NACís used for Tylenol over-dose).  Q:  Any evidence that viruses are mimicking the genes? A:  There are some cerebral problems caused by virus.  There are viruses or immune system reactions that can cause cerebellum problems.  Genetic processes come on very slowly (years) v. virus processes (months).  Q:  Is there is a possible of reversing damage, when treatment is available? A:  There will be some recovery based on ìwoundedî  mitocondrial healing . Further understanding of nerve growth factors may help with FA treatments. Or, stem cell transplants might help (need very immature cells).  Q:  High dosages of CoQ10?  400 Mg of CoQ10, w/2000 IU of Vit E (UK trial) A:  Itís unclear they get into the brain (Idebenone is smaller).  Itís unclear what the right dosage is.  Q:  Neuroten & silegeline. (sp??) A:  Used for nerve related pain.  Anti-fatigue medication.  Q:  NAC - why no recent (today) discussion about NAC. A:  There were some small, un-controlled studies a number of years ago. Weíre just now seeing the animal studies in NAC.  Q:  Should we try Idebenone? A:  For cardiac & neurological affect - CoQ10 seems to work, NAC unclear, itís too early for Idebenone.  Q:  Chronic mouth outbreaks & high Vitamin C dosages. A:  High dosages of C does increase iron absorption (500 Mg is not high - 1,000 Mg may be high, causing increased absorption of iron). Have a blood test to determine iron saturation levels.    Home    Index    Page1    Page2    Page3    Page4