SET-HD Update August 2005

The SET-HD working group is continuing to prepare detailed reviews of the approximately 40 compounds selected for initial evaluation based on their potential to move quickly into clinical trials. Reviews of the first group of these compounds are now complete and available for review. These 24 reviewed compounds include those which have been tested in transgenic mice as well as three compounds that have been tested in humans but not in transgenic mice (Amantadine, Memantadine, and OPC-14117). An article summarizing these reviews is currently in process. These data are available to help plan HD clinical trials.

Meanwhile, in addition to preparing compound reviews, the SET-HD working group is extending its strategy to help facilitate compound preclinical development and will soon be announcing plans to expand its efforts. Stay tuned for more information.

SET-HD Update February 2005

The SET-HD working group is continuing to prepare detailed reviews of the approximately 40 compounds selected for further consideration. The first ten of these reviews are now complete. These 40 compounds are thought to have the greatest potential to move quickly into clinical trials. For each of these compounds, one or more members of the working group reviewed the literature to assess and report on:

· Mechanism of action (MOA)

· Scientific rationale
· Animal model data

· Pharmacokinetics (including blood brain barrier penetration)

· Safety and tolerability in humans
· Drug interaction potential

· Clinical trial evidence in humans (if any)

· Dosage recommendations

The reviewers also made suggestions about the next steps that should be taken to move this compound forward toward clinical trials in humans.

Reviews for the following ten compounds have been prepared and can be reviewed by clicking on the links below:

Over the next several months, reviews will be prepared and posted here for all 40 of the compounds selected in this first round.

SET-HD Update December 2004

The SET-HD working group has begun the process of preparing detailed reviews of the approximately 40 compounds

· Mechanism of action (MOA)

· Scientific rationale

· Animal model data

· Pharmacokinetics (including blood brain barrier penetration)

· Safety and tolerability in humans

· Drug interaction potential

· Clinical trial evidence in humans (if any)

· Dosage recommendations

The reviewers also made suggestions about the next steps that should be taken to move this compound forward toward clinical trials in humans.

Reviews for the following five compounds have been prepared and can be reviewed by clicking on the links below:

Over the next several months, reviews will be prepared and posted here for all 40 of the compounds selected in this first round.

On May 19^th, the SET-HD working group met in Washington DC to begin the process of prioritizing the nearly 200 compounds that had been nominated as potential interventions against HD. The goal of this meeting was to identify promising candidates that have the greatest potential to move into clinical trials quickly. The group identified approximately 40 compounds for further consideration. These compounds have not been selected for clinical trials, but will undergo further review and scrutiny so that the most appropriate candidates for clinical trials can be identified. These agents are not recommended for use by people with HD and medications should only be taken in consultation with a treating physician.

Selection methods were hierarchical and considered according to the following criteria:

• Drugs ready for human HD clinical studies based on previous studies showing safety and tolerability in humans; or on relevant data collected for an investigational new drug application (IND) that demonstrated readiness for human studies.
  
• Rationale for use in HD, including results from animal studies that indicate efficacy; or compelling evidence from studies in invertebrates or in vitro models suggesting potential activity relevant for HD; or known clinical activity based on previous clinical use.
  

  • Nominations of multiple compounds of the same class were reduced to a manageable number by consideration of secondary criteria such as pharmacokinetics and achievable brain concentrations in order to allow consideration of a wide range of compounds.

  Compounds For Review
  

  
  

  
  

  
  What does “selected for further consideration” mean?

  
  

  Compounds selected for further consideration will undergo more detail evaluation to find out if they fulfill the operational criteria that were established by the Huntington Project in order to identify compounds likely to make a difference in the lives of people with HD.

  
  

  What does not being selected mean?

  
  

  Nothing has been excluded in this search for effective treatments. Many compounds did not make the “short list” only because there was insufficient information available. Other well-known agents have been well described and characterized in other settings and do not need in-depth reviews from SET-HD for the purposes of informing clinical studies. In the future, the working group will reevaluate compounds that were nominated but not selected in this round. Individuals who wish to submit additional information about specific compounds are encouraged to do so on the nomination form.

  
  

  What compounds have been nominated?

  
  

  A complete list of compounds nominated in the first round (through March 31, 2004) is available for viewing. You can still NOMINATE A COMPOUND for future consideration.

  
  

  We invite your comments about these selections and the SET-HD process.

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  SET-HD Update May 2004

  
  

  As of March 31, 2004, the SET-HD web site received over 200 nominations of potential interventions for HD. These compounds are now being evaluated by the SET-HD working group in order to identify those with the greatest potential to move rapidly into clinical trials.

  
  

  The first round of evaluations will focus on agents that have enough safety information to be used in clinical trials in HD in the near future. The intent is to advance the most promising agents whether they are for neuroprotection or symptomatic/ palliative treatment.

  
  

  All agents will be characterized according to the following criteria: rationale and mechanism, consistency of pre-clinical data, pharmacokinetics and ability to reach the brain in relevant concentrations, and evidence of efficacy in HD animal models. Those people who nominated compounds will be asked to review and comment on the evaluation. Evaluations will be available for review on this web site, and will be published in a peer-reviewed journal.

  
  

  The first round of evaluations is expected to be complete by 4^th quarter of 2004. Subsequent rounds of evaluations will include agents that appear promising because of their particular mechanism of action, even though they may not yet have been tested in humans. The SET-HD working group will identify steps that are needed to develop agents that have not yet made it to human trials.

  
  

  Compounds may still be nominated through the SET-HD web site. SET-HD is an ongoing process aimed at identifying important treatments for HD.

  
  

  We will continue to update this site about the progress of SET-HD.

  
  

  SET- HD Working Group:

  
  

  NINDS: Bernard Ravina, MD, Jill Heemskerk, PhD, Diane Murphy, PhD, Kenneth Fischbeck, MD, Nicholas DiProspero, MD, PhD, Robert Hart, MD

  
  

  Academic Investigators: Susan Fagan, PharmD, Collin Hovinga, PharmD, Louis Profenno, MD, PhD, Madeline Harrison, MD

   

  Patient Advocate: James A. Tretheway