Louie, RR: Comments on the “nexus” meeting report regarding dementia and cancer, letter to editor, Alzheimer’s and Dementia, 2017; 13:720-21; DOI: 10.1016/j.jalz.2017.03.005

 

Dear Editors:

Comparing disease research in dementia and cancer provides ready similarities and contrasts, even though one condition is generally thought of as tissue degeneration, and the other as tissue proliferation.  Yet each disease can be devastating and fatal.  Snyder et al provided a summary of the “Nexus” meeting, which explored those comparisons 25 May 2016, sponsored by the Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation [1].

One stark contrast is the armamentarium of effective therapies available in the two conditions.  Over the last five years, the FDA has approved only one drug for Alzheimer’s Disease (AD),  a pill that basically combines two older agents; in the same time frame, 70 cancer agents or indications were approved [2, 3].

The meeting agenda included a discussion of therapeutic implications; drug repurposing is mentioned in the review.  However, the meeting may have missed an opportunity to explore how clinical research has been performed differently in the cancer and dementia arenas, and ways to improve AD outcomes by enhancing therapeutic, rather than basic, research.

There is no doubt that the pace of cancer progression, concrete measures such as survival, consensus “biomarkers” in readily available routine lab work and imaging, along with funding, have had positive impacts in oncology.   Cancer clinical trials outnumber Alzheimer or dementia trials by almost 40-fold, but they are also effectively executed in oncology, relying on a vast infrastructure that does not have a parallel in dementia work.

For example, the Children’s Oncology Group (COG), funded yearly at only $25M, coordinates nearly 100 clinical trials at 200 pediatric cancer units across three continents.  These include Phase I, II and III trials for relatively rare diseases.  The group has a research portfolio that includes cancer biology, drug development, supportive care and survivorship. COG’s history and success is documented; it has benefitted from strong leadership and bold, directed strategies [4].

Many early cancer trials combined agents in various permutations, and tested agents approved in adult cancer, basically drug repurposing. We still lack full mechanistic explanations of many of the pathways in carcinogenesis, or the exact mechanism of action of many essential agents. The point is that therapeutic efforts did not wait.

The survival rate for the most common childhood leukemia has gone from less than 10% in the 1960’s to over 90% now, with incremental progress every five years.  Most kids are cured with combination chemotherapy that was developed empirically decades ago, before sophisticated molecular testing or genetic targets [5]

The National Alzheimer Project Act produced goal-oriented Milestones documents in 2013 and 2016. The latest update did not report any therapeutic success [6]. However, the NIA Bypass Budget 2017 (from 2015 directs only 29% of funds to translational, clinical interventions research, while 71% goes to genetics, imaging, and other areas not directly therapeutic [7].

Clinical trials are necessary for improvement in AD outcomes for patients; to that end the NIA recently created a Clinical Trials Toolbox. The Milestones do call for other improvements; others have pointed out how clinical strategies could be improved [8, 9]. One critical feature that seems to be consistently missing is a concrete plan to develop assertive and accountable clinical leadership to achieve those improvements.

AIDS therapy, like cancer, is an area of medicine that has seen great progress in a relatively short time.  The leadership of Dr. William Paul, an “AIDS Czar,” is credited with accelerating clinical progress in that condition.  Still incurable, nevertheless AIDS patients’ lives are now extended from months to years [10].

The appointment of a “dementia czar,” specifically for therapy, might facilitate overall strategy, trial coordination, consensus trial templates, informed consents, vigorous subject recruitment and infrastructure development, perhaps modeled on cancer trials groups. Comprehensive planning for repurposing and combination therapy trials, mentioned in the meeting review and by others, would seem like an ideal place to start.

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Respectfully,

Ronald R. Louie, MD

  1. Snyder HM, Ahles T, Calderwood S, Carrillo MC, Chen H, Chang CH, Craft S, De Jager P, Driver JA, Fillit H, et al, Exploring the nexus of Alzheimer’s disease and related dementias with cancer and cancer therapies: A convening of the Alzheimer’s Association & Alzheimer’s Drug Discovery Foundation. Alzheimers Dement. 2016 Dec 18. pii: S1552-5260[16]33090-4. doi: 10.1016/j.jalz.2016.11.002. [Epub ahead of print]
  2. https://www.centerwatch.com/drug-information/fda-approved-drugs/therapeutic-area/10/neurology. Accessed January 4, 2017.
  3. https://www.centerwatch.com/drug-information/fda-approved-drugs/therapeutic-area/12/oncology.  Accessed January 4, 2017.
  4. O’Leary M, Krailo M, Anderson, JR and Reaman GH, Progress in Childhood Cancer: 50 Years of Research Collaboration, A Report from the Children’s Oncology Group. Semin Oncol. 2008 Oct; 35[5]: 484–493.
  5. Hunger SP and Mulligan CG, Acute Lymphoblastic Leukemia in Children, N Engl J Med 2015; 373:1541-1552 October 15, 2015 DOI: 10.1056/NEJMra1400972
  6. https://aspe.hhs.gov/advisory-council-february-2017-meeting-presentation-transforming-alzheimers-disease-therapy-development . Accessed March 21, 2017.
  7. https://niaprodfiles.s3.amazonaws.com/s3fs-public/reaching-for-a-cure-alzheimers-disease-and-related-dementias-research-at-nih.pdf. Accessed February 17, 2016.
  8. Fargo KN, Aisen P, Albert M, Au R, Corrada MM, DeKosky S, Drachman D, Fillit H, Gitlin L, Haas M, et al, 2014 Report on the Milestones for the US National Plan to Address Alzheimer’s Disease. Alzheimers Dement. 2014 Oct;10[5 Suppl]:S430-52.
  9. Cummings J, Aisen PS,DuBois B, Frölich L, Jack, CR, Jones RW, Morris JC,Raskin J, Dowsett SA and Scheltens P, Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016; 8: 39.
  10. Roberts S, Dr. William E. Paul, Who Helped AIDS Research Save Millions of Lives, Dies at 79. New York Times, 2015, Sept. 22.

[NIH public domain image: technician and person in MRI]