News Brief: Scientists Net Prizes for Progress Toward ALS Biomarker

The nonprofit Prize4Life is awarding two scientific teams with $50,000 each at the American Academy of Neurology annual meeting in Seattle, Washington, this week. Both groups have made significant progress in defining biomarkers for amyotrophic lateral sclerosis that could be used to track the disease in clinical trials. Harvey Arbesman, a dermatologist in Buffalo, New York, and collaborators found that skin elasticity declines in step with disease progression. Seward Rutkove of Harvard Medical School led a group that proposed measuring how electricity flows through muscle as a marker for worsening ALS. Prize4Life is offering a $1 million award for a biomarker that will slash the costs of clinical trials; so far, no one has presented strong enough data to claim the full prize.

Currently, scientists have few methods to determine if a drug is effective in slowing the degeneration of motor neurons in people with ALS. Clinical trials rely on survival and loss of respiratory function as outcomes. “Those are very late measures,” said Melanie Leitner, chief scientific officer of Prize4Life, so trials last for 15 months or more and can cost $8-$10 million.

Prize4Life was founded in 2005 to accelerate research on ALS treatments. The organization has adapted the model of the X-Prize (best known for sponsoring prizes for space travel and DNA sequencing), and the government H-Prize for renewable energy, to accelerate research breakthroughs in ALS. Its ALS Biomarker Prize Challenge, running since 2006, offers $1 million for an innovative biomarker that will cut trial costs in half. (Prize4Life also funds this reporter’s position with ARF.)

Programs such as the ALS Biomarker Prize Challenge encourage “out-of-the-box” thinking, Arbesman said. The Challenge inspired Arbesman to delve into the ALS literature, where he discovered that people with ALS have decreased skin elasticity. Arbesman, collaborating with neurologists at Columbia University in New York, tested a skin elasticity measurement device commonly used in the cosmetics industry. The method is quick and painless. They found that 30 people with ALS had lower elasticity than a control group of 40 caregivers, and that elasticity declined as a person’s score on the ALS Functional Rating Scale decreased. Arbesman presents his results today at the Seattle meeting and plans to publish his work once analysis of the six-month follow-up data is complete.

Rutkove, a Harvard neurologist working in collaboration with physicists at Northeastern University in Boston, has been developing methods to measure muscle conductivity for the past decade. Current flow through muscle is altered in diseased tissue. Rutkove has shown that electrical impedance myography, a noninvasive technique, provides results comparable to and possibly better than the ALS Functional Rating Scale (see Rutkove et al., 2007). Rutkove, who has been working with methods not specifically designed for direct muscle measurements, hopes to improve the available technology toward that end. “The thing that I really want to move forward is the device development aspect,” he said.

Prize4Life reviewed 12 entries from seven countries, and these two teams stood out because they came close to fulfilling the prize criteria. “These teams hadn’t gotten 100 percent of the way…but our Scientific Advisory Board felt that they had really gotten 75 percent, 80 percent of the way,” Leitner said. Given more data, “they have a very strong chance of passing the bar,” she said.

The Challenge will reopen for submissions 15 May, with a rolling deadline until October 2010.—Amber Dance.

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References

Paper Citations

  1. Rutkove SB, Zhang H, Schoenfeld DA, Raynor EM, Shefner JM, Cudkowicz ME, Chin AB, Aaron R, Shiffman CA. Electrical impedance myography to assess outcome in amyotrophic lateral sclerosis clinical trials. Clin Neurophysiol. 2007 Nov;118(11):2413-8. PubMed.

External Citations

  1. Prize4Life

Further Reading

Papers

  1. Rutkove SB, Aaron R, Shiffman CA. Localized bioimpedance analysis in the evaluation of neuromuscular disease. Muscle Nerve. 2002 Mar;25(3):390-7. PubMed.
  2. Mitchell RM, Freeman WM, Randazzo WT, Stephens HE, Beard JL, Simmons Z, Connor JR. A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. Neurology. 2009 Jan 6;72(1):14-9. PubMed.
  3. Kasai T, Tokuda T, Ishigami N, Sasayama H, Foulds P, Mitchell DJ, Mann DM, Allsop D, Nakagawa M. Increased TDP-43 protein in cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Acta Neuropathol. 2009 Jan;117(1):55-62. PubMed.
  4. Ryberg H, Bowser R. Protein biomarkers for amyotrophic lateral sclerosis. Expert Rev Proteomics. 2008 Apr;5(2):249-62. PubMed.

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