Donation of Tissue for Research

Donation of tissue is very important for researchers, particularly the brain and spinal cord to find the treatment and cure of ALS.

If you'd like to donate such tissue after death, contact the:

University of Miami
School of Medicine
Department of Neurology
Julie Steele
305-243-7424

The Therapeutic Trials Division is under the direction of Dr. Walter Bradley and the Research Coordinator, Julie Steele. The team includes Dr. Khema Sharma, two fellows in neuro-muscular disease, Drs. Robin Kass and Julie Schwartzbard, Angela Anderson, Doris Martin and Barbara Fitzgerald.

We currently have 57 patients involved in the Sanofi Drug Trail, 9 in the BDNF Extension Trial and 6 in the Myotrophin Early Release Program.

The Sanofi Trail is of an oral agent which in the test tube and in experimental animals improves motor neuron function by stimulating neurotrophins (nerve growth tactors). Dr. Bradley is a member of the Steering Committee of the trial, wliich is being carried out in 54 centers in North Armerica and Europe. The total number of patients taking part in this study is over 2,000. The trial started in 4/97 and the 18 months of treatment for the last patient will be completed around 5/99. Like all clinical trials, this is a double-blind controlled study, and neither the patients nor the doctors know who is receiving active and who is receiving placebo. This is a very important part of the process to deterinine if a drug works and whether it is safe or dangerous.

The BDNF Extension Study is run under the direction of Dr. Walter Bradley for patients who previously took part in the double-blind controlled trial of

BDNF in ALS. We are supervising the continuing treatment with BDNF of patients in centers around North America. Analysis of the main trial of BDNF did not show a benefit, but later a study of the results indicated that there were some patients that did appear to be assisted, with slowing down of the progress of the disease. It seems likely that two new studies of BDNF will be mounted in the coming year, one of a higher dose of BDNF, given subcutaneously, and the other of BDNF administered by intrathecal injection via an implanted subcutaneous pump (like a pacemaker).

The Myotrophin Early Access Program has allowed a small number of patients to enter through a lottery to receive subcutaneous Myotrophin, while the company and the FDA decide whether a further trial of the drug to determine if it is beneficial or not is needed.

Dr. Bradley is one of the Steering Committee of the World Federation of Neurology Clinical Trials Consortium. This body chaired by Professor Michael Swash of the London Hospital and Dr. Theodore Munsat of Tufts New England Medical Center held a meeting from March 31 to April 2, 1998, at Airlie House, Virginia, to develop new guidelines for clinical trials and new criteria for the diagnosis of ALS. The goal of these new criteria is to allow the disease to be recognized for research purposes at an earlier stage than has previously been the case, so that patients can be admitted to trials early in the course of their disease. These new guidelines and criteria are likely to be applied in forthcoming clinical therapeutic trials in ALS.

The Clinical Trials Division is also undertaking studies in spinal muscular atrophy and clystonia.

There are many theories about what causes ALS, and what leads to progression of the disease. In the last year or so, these theories have concentrated into two main areas, one is the glutamate theory: there appears to be too much glutamate in the nervous system of patients with ALS, that over-stimulates the nerve cells and produces neuronal death. The other

is the free radical oxidative damage theory: the normally occurring free radicals and highly reactive oxygen species are not handled property, accumulate in the nerve cells and bring about their death. We and a number of other centers around the world have begun to develop techniques to investigate these two theories in the living brain. In patients with ALS and their spouses, we are undertaking a study of magnetic resonance spectroscopy to look at chemicals in the brain. This technique is a way of using an MRI inachine to identily the concentration of cheniicals in the brain. Studies show a fall in the arnount of a compound NAA which is a marker of nerve cells. This may in part be due to the death of the motor nerve cells and in part because they are sick. Preliminary studies suggest that there may be a return towards normal in NAA concentration in patients treated with Riluzole. We are also investigating glutamate concentration in the brain of ALS patients, and comparing this with their spouses. So far the results are complex, and we recently had a meeting in Airline House, Virginia with experts from all over the world in a meeting sponsored by the ALS Association to acivance MR spectroscopy research in ALS.

We have taken these findings to the research laboratory with two brilliant young research workers in the Department of Neurology. Dr. Miguel Perez-Pinzon is investigating how glutamate levels are controlled in the brain, using experimental animals. We have a colony of mice who suffer from a motor neuron disease-like condition, called the wobbler mice. We are also administering drugs to animals to try to alter the level of glutamate in the brain. Dr. Carlos Moraes, an internationally renowned research worker in mitrochondria, is investigating oxidaitive metabolism and the role of mitrochondria. He is studying mitrochondria from the platelets of patients with ALS, and also animal models of the disease.

Research is always a long-term investment. The answers usually do not come out how you expect them. Often no worthwhile results come out and you have to go back to the drawing board. However, without research, we will never have progress. Without brilliant research workers, we will never have any hope of finding the cause of this disease.