Research at Day Lab

Cecil B. Day Laboratory for Neuromuscular Research

The Cecil B. Day Laboratory for Neuromuscular Research was founded in 1983 to investigate genetic defects that cause neuromuscular paralysis. The focus of the initial investigations was a rare form of muscular dystrophy known as Miyoshi myopathy. A second disease that has been extensively studied in the Day Lab is Lou Gehrig’s Disease, or amyotrophic lateral sclerosis (ALS). Other research topics include periodic paralysis, a sensory-motor neuropathy (HSN1) and a form of adrenoleukodystrophy (Lorenzo’s Oil Disease). In each disease category, the initial research goal has been to identify primary gene defects that can cause these disorders. In each case, investigators in the Day Laboratory have been fortunate to participate in the discovery of underlying gene defects. The laboratory is now generating animal and Petri dish models of each disease as a first step toward developing treatments.

Visit the Cecil B. Day Lab page at UMass Medical

Development of RNAi Therapy for the treatment of amyotrophic lateral sclerosis (ALS)

Dr. Robert Brown, Professor and Chair, Department of Neurology is one of the world’s authorities on ALS. Dr. Brown’s laboratory identified one of the genes associated with ALS, cytosolic superoxide dismutase, or SOD1. Current views suggest that the mutation of SOD1 causes misfolding of the SOD1 protein and resulting toxicity to the neuron. 

Recent studies by Dr. Zuoshang Xu, Professor of Biochemistry and Molecular Pharmacology have demonstrated that RNAi molecules can silence mutant SOD1 in vivo and increase survival time in the mouse model of ALS. Drs. Brown and Xu have collaborated in the design of RNAi molecules for a trial in humans with mutant SOD1 associated ALS. First in human studies of RNAi in ALS are currently underway at UMass.

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Because of the support of The Angel Fund family, we have helped in the funding of major ALS breakthroughs!

A note from Dr. Robert H. Brown:

All of us in the ALS research program at UMass Medical School remain extremely grateful to you for your continuing support.  This year we are particularly excited to report that we are now engaged in an all-out effort to move our treatment program from the lab to the bedside.  Specifically, we have been working for more than five years on technology to turn off one of the most important ALS genes, known as SOD1.  We have now succeeded in turning down the activity of the offending gene in mice and most recently in larger animals.  Our hope is to be able to approach the FDA by  mid-summer with a discussion of what additional studies will be needed to try this therapy in our friends in the clinic with this type of ALS.

Equally importantly, we now have effective models for two other types of ALS, caused by mutations in other genes such as the new gene C9orf72.  We believe that the strategies we are pursuing now for SOD1 will be effective for the C9orf72 cases.  And, with collaborators, we are also gearing up to move forward a related strategy to treat types of ALS arising from mutations in the genes FUS and TDP43.
We recognize that these familial cases are, fortunately, not the most common forms of ALS, but we have reasons to anticipate that the strategies we develop for these gene silencing projects in familial ALS will also work for sporadic ALS.
I should note two other points.  First, the above programs all involve gene therapy for the delivery of the key therapies to the interior of the spinal cord.  We also have an active program to use more conventional mediations (so-called “small molecules”) to achieve the same type of gene silencing.  These programs are making headway as well.  Second, the UMass team has also continued its longstanding efforts to find new ALS genes.  The team, including my lab and the labs of John Landers, Daryl Bosco, Larry Hayward, and Fen-Biao Gao, has identified two new genes this year; there are now more than 35 ALS genes identified.  Dr. Landers in particular has organized a very productive effort in this regard.   We very much hope that the therapies we are developing will be broadly applicable to this family of ALS genes.

On behalf of all of us in the ALS labs at UMMS, our heartfelt thanks to The Angel Fund.

Thank you for your support!!!

We will find the cure!!