Research

Gene Science

The ADCY5 gene encodes for adenylyl cyclase V, a member of a family of proteins responsible for generating cyclic adenosine monophosphate (cAMP) in cells. The regulation of cAMP levels is important because cAMP is a messenger that helps regulate levels of sugar and lipids in the body and mediates skeletal muscle processes. In addition, ADCY5 is highly expressed in the striatum, a region in the brain that is involved in modulating movement. A study of mice lacking the ADCY5 gene, shows that the absence of the gene causes a motor disorder similar to Parkinson’s disease. ADCY5 has been shown to be important in balancing and maintaining both coordination and locomotion and in responding to stimulation by dopamine neurotransmitters.

Rare Science and CIRM (CA Institute for Regenerative Medicine) partnered to create stem cells for 13 families affected by ADCY5 variants. Rare Science is a non-profit that helps rare disease organizations understand and leverage the latest science for their disease’s unique needs.

Rare Science received support from CIRM’s induced pluripotent stem cell (iPSC) initiative to create stem cells for individuals with ADCY5 mutations and their family members. This stem cell project with Rare Science and CIRM will remove the time, hassle, and expense related to generating stem cells. Researchers can now focus on the biochemistry and molecular biology of ADCY5 variants. The stem cells will be stored at the Coriell Institute and sold with NO intellectual property reach back conditions for a nominal fee to academics and researchers via the Coriell website.

Rare Science, CIRM, and ADCY5.org are truly blazing new trails in the Rare Disease world with this one-of-a-kind project.

Tara Schmidlen at Coriell has written two blog posts about the importance of biobanking and how storing samples and sharing them with the research community is benefitting Rare Disease.

Banking for the Future: How Biobanking Helps the Rare Disease Community

Biobanking on the Future: How Biobanking Supports Research

Journal Articles

Scoping review on ADCY5-related movement disorders. Movement Disorders Clinical Practice 2023 in press. Menon JP, Nilles C, Silveira-Moriyama L, Yuan R, de Gusmao CM, Münchau A, Carecchio M, Grossman S, Grossman G, Méneret A, Roze E*, PringsheimT*. https://pubmed.ncbi.nlm.nih.gov/37476318/

Effects of theophylline on ADCY5 activation-From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients Tänzler D, Kipping M, Lederer M, Günther WF, Arlt C, Hüttelmaier S, Merkenschlager A, Sinz A. PLoS One. 2023 Mar 3;18(3):e0282593. doi: 10.1371/journal.pone.0282593. eCollection 2023. PMID: 36867608

Efficacy of caffeine in ADCY5-related dyskinesia: a retrospective study. Movement Disorders April 2022 Méneret A, Mohammad SS, Cif L Doummar D, DeGusmao C, Anheim M, Barth M, Damier P, Demonceau N, Friedman J, Gallea C, Gras D, Gurgel-Giannetti J, Innes EA, Necpál J, Riant F, Sagnes S, Sarret C, Seliverstov Y, Paramanandam V, Shetty K, Tranchant C, Doulazmi M, Vidailhet M, Pringsheim T, Roze E.

Vijiaratnam N, Newby R, Kempster PA. Depression and psychosis in ADCY5-related dyskinesia – part of the phenotypic spectrum? J Clin Neurosci. 2018;57:167-168. https://www.ncbi.nlm.nih.gov/pubmed/30172639

Carecchio M, Mencacci NE, Iodice A, et al. ADCY5-related movement disorders: frequency, disease course and phenotypic variability in cohort of paediatric patients. Parkinsonism Relat Disord. 2017;41:37-43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549507/

Douglas AGL, Andreoletti G, Talbot K, et al. ADCY5-related dyskinesia presenting as familial myoclonus-dystonia. Neurogenetics. 2017;18:111-117. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359383/

Dy ME, Chang FC, Jesus SD, et al. Treatment of ADCY5-associated dystonia, chorea, and hyperkinetic disorders with deep brain stimulation: a multicenter case series. J Child Neurol. 2016;31:1027-1035. https://www.ncbi.nlm.nih.gov/pubmed/27052971

Chang FC, Westenberger A, Dale RC, et al. Phenotypic insights into ADCY5-associated disease. Mov Disord. 2016;31:1033-1040. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950003/

Chen DH, Meneret A, Friedman JR, et al. ADCY5-related dyskinesia: broader spectrum and genotype-phenotype correlations. Neurology. 2015;85:2026-2035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676753/

Mencacci NE, Erro R, Wiethoff S, et al. ADCY5 mutations are another cause of benign hereditary chorea. Neurology. 2015;85:80-88. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501937/

Chen YZ, Friedman JR, Chen DH, et al. Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.
Ann Neurol. 2014;75:542-549. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457323/

Kawarai T, Orlacchio A, Kaji R. Lesser motor disability in adulthood: A ten-year follow-up of a dyskinetic patient with ADCY5 mutation. J Neurol Sci. 2019 Oct 15;405:116383. doi: 10.1016/j.jns.2019.07.001. Epub 2019 Jul 31. PMID: 31422281. Méneret A, Gras D, McGovern E, Roze E.

Caffeine and the Dyskinesia Related to Mutations in the ADCY5 Gene. Ann Intern Med. 2019 Sep 17;171(6):439. doi: 10.7326/L19-0038. Epub 2019 Jun 11. PMID: 31181574. Doyle TB, Hayes MP, Chen DH, Raskind WH, Watts VJ.

Functional characterization of AC5 gain-of-function variants: Impact on the molecular basis of ADCY5-related dyskinesia. Biochem Pharmacol. 2019 May;163:169-177. doi: 10.1016/j.bcp.2019.02.005. Epub 2019 Feb 14. PMID: 30772269; PMCID: PMC6470011. Vijiaratnam N, Newby R, Kempster PA.

Depression and psychosis in ADCY5-related dyskinesia-part of the phenotypic spectrum? J Clin Neurosci. 2018 Nov;57:167-168. doi: 10.1016/j.jocn.2018.08.049. Epub 2018 Aug 30. PMID: 30172639. Balint B, Antelmi E, Mencacci NE, Batla A, Eriksson SH, Walker MC, Bronstein AM, Bhatia KP.

Oculomotor apraxia and disrupted sleep with nocturnal ballistic bouts in ADCY5-related disease. Parkinsonism Relat Disord. 2018 Sep;54:103-106. doi: 10.1016/j.parkreldis.2018.04.011. Epub 2018 Apr 10. PMID: 29680308. Tunc S, Brüggemann N, Baaske MK, Hartmann C, Grütz K, Westenberger A, Klein C, Münchau A, Bäumer T.

Facial twitches in ADCY5-associated disease - Myokymia or myoclonus? An electromyography study. Parkinsonism Relat Disord. 2017 Jul;40:73-75. doi: 10.1016/j.parkreldis.2017.04.013. Epub 2017 Apr 20. PMID: 28442302.