Research Update

Update on Current Research
By Florian Eichler, M.D. Massachusetts General Hospital

HSAN1 Trial Update: The two-year, double-blind, placebo-controlled trial studying the efficacy of L-serine in patients with HSAN1 is well underway. Eighteen individuals enrolled to date. Sixteen subjects were enrolled between mid-September and early December. Two more were enrolled in early April. To date, 16 subjects have completed their 6 month follow-up visit. We need two more subjects to reach our target enrollment of 20. No adverse effects have been attributed to L-serine.

The study is randomized to placebo versus study drug, and the investigators are blinded to who is on placebo and who is on study drug. Therefore we cannot at this point report any conclusions. However, we hope that in the second year, data analysis will allow us to report some insights. A full assessment will not be possible until all patients have completed the two year trial.

As HSAN1 is thought to be to a rare disease, we have been surprised at the rapid enrollment. We credit the Deater Foundation greatly for their support and attribute the successful enrollment to date in large part to their effort. It also shows that trials bring about greater disease awareness and patient engagement. We hope this momentum will sustain and help recruit the remaining two patients needed.

Soon to be published study on the Natural History of HSAN1: In a recent collaborative natural history study between MGH and UMass, we found that while standard nerve conduction studies are reliable in assaying large fiber function in HSAN1, they do not adequately measure small fiber function. This is because these small fibers do not contribute to main components of nerve conduction studies. We found that the best objective diagnostic tests for small fibers are distal-leg skin biopsies that assess density of small-fiber skin innervation.

New Center Initiative at MGH: Recently, MGH has become part of the CMT Rare Diseases Clinical Research Network (RDCRN). HSAN1 has the potential for broad impact in the field of hereditary neuropathies. We are glad that through participation in this consortium we will be able to communicate our insights in HSAN1 more effectively. The CMT community has the ability to make patients and physicians more aware of HSAN1.

Natural History in Children of Patients with HSAN1: During the last HSAN1 meeting, many of the investigators were enthusiastic about proceeding with a natural history study in children of patients with HSAN1. At the time the thought was to study all children regardless of whether they carried the mutation or not. This would prevent difficult ethical issues as well as allow for an important control group. However, the IRB application and study documents are still preliminary and have not been finalized. We look forward to a natural history study in children of patients with HSAN1. We will work with Drs. Brown, Oaklander and Fawn Leigh, a pediatric neurologist with neuromuscular expertise at MGH, to accomplish this goal. We are poised to carry out this study, but will need continued support from the Deater Foundation to make this possible.

Lastly, we give many thanks to:

  • Dr. Oaklander, Dr. Novak, Dr. David, and Dr. Fridman. Thank you for your expert assistance with the trial.
  • The Deater Foundation. Participation from the family has been extraordinary and contributes greatly to the success of this trial. Elise Johnson (coordinator) states that it has been a pleasure to work with each and every individual in the trial. She thanks them for their dedication and positive support. The MGH neurogenetics DNA diagnostics laboratory. HSAN1 trial brochures were mailed to all individuals that tested positive for HSAN1. The lab’s assistance in recruitment allowed us to discover another individual with HSAN1 who is currently enrolled in the trial.