Michael Mullan

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Michael Mullan
Michael Mullan whitfield sarasota Florida.jpg
Mullan describing how the Brain Reserve Index works
Born
Michael John Mullan

(1956-11-14) November 14, 1956 (age 67)
Farnborough, Kent, U.K.
Years active1985–present
Title
Website www.mullanalzheimer.com

Michael Mullan is an English-American researcher in Alzheimer's disease and related neurodegenerative disorders. [1] Mullan was a co-discoverer of genetic causes of Alzheimer's disease. Subsequently, he was a co-inventor on the original patents [2] [3] that covered three mutations in the amyloid precursor protein (APP) gene, a gene which is linked to familial Alzheimer's disease. He also co-authored articles in Nature and Nature Genetics, describing these three genetic errors; [4] [5] [6] he was the senior author on two of those articles. [5] [6] Dr. Mullan co-discovered a specific genetic mutation, which became known as "the Swedish Mutation," [6] because it was originally identified in DNA samples from two Swedish families whose members often developed early-onset Alzheimer's disease. These human genetic mutations were integrated into mouse DNA to create strains of mice (transgenic animal models) that are being used worldwide to develop new drug treatments for Alzheimer's disease.

Contents

Mullan was trained as a physician in England receiving his medical degree from the Royal Free Hospital, London University. As a physician, he won a clinical research fellowship in the UK and subsequently gained a PhD in molecular genetics, also from London University. In the UK and US he specialized in the diagnosis and treatment of Alzheimer's disease. He has co-authored over 200 papers on Alzheimer's disease and related disorders—on many of which he served as senior author. He has held positions as Professorial Chair and positions as professor of psychiatry, Neurology, and Pathology. He cofounded the Roskamp Institute, [7] a not-for-profit, stand-alone biomedical research Institute and was its Director and CEO. Mullan was the CEO and chairman of Rock Creek Pharmaceuticals. [8] Mullan is the CEO of Archer Pharmaceuticals, [9] a for-profit spin-off of the Roskamp Institute. His work has focused on the development of new treatments for inflammatory disorders, particularly of the brain, with the ultimate goal of "reducing the burden of human suffering" associated with these diseases.

Co-founding the Roskamp Institute

Mullan and Crawford cofounded the Roskamp Institute with developer and philanthropist Mr. Robert Roskamp in Sarasota Florida in 2003. [10] [11] [12] Mullan and Crawford wanted to name the institute after Mr. Roskamp and his family in recognition of their extensive contributions to the advancement of scientific research to find new treatments for neurological and psychiatric disorders. The institute was established as a standalone biomedical state-of-the-art research facility to find the causes and new treatments for neuropsychiatric conditions. [13] [14] In the mission statement of the Institute Mullan chose the phrase "to reduce the burden of human suffering" in reference to the mental and physical devastation that such conditions as Alzheimer's cause. The institute is a multicultural multi-ethnic research environment combining a wide variety of expertise in molecular and cell biology, genetics, proteomics, lipidomics, medicinal chemistry, drug discovery and development. The institute is a not-for-profit public charity funded variously by national peer-reviewed grants from the Department of Defense, the NIH, the Veterans Administration and other agencies.

Under the directorships of Mullan and Crawford the Roskamp Institute focuses on discovering new treatments for Alzheimer's disease, [12] traumatic brain injury, [15] multiple sclerosis, [16] Gulf War illness [17] and other central nervous system disorders.

Swedish mutation patent litigation

The patents covering the Swedish Mutation were the subject of extensive litigation due to their commercial value. In one case brought by AIA against Eli Lilly (in which Mullan was an expert witness) the United States District Court for the Eastern District of Pennsylvania found that another individual, John Hardy was a co-inventor on the Swedish mutation patent. [18] The patent was initially filed listing Mullan as the sole inventor at Hardy's suggestion (Hardy was Mullan's PhD supervisor). Hardy was employed by Imperial College at the time. This strategy successfully allowed Lilly and Avid to invalidate the patent. British patent law stipulates that such inventions would be owned by the employer and not the employee. [19]

Related Research Articles

<span class="mw-page-title-main">Amyloid beta</span> Group of peptides

Amyloid beta denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.

<span class="mw-page-title-main">Amyloid-beta precursor protein</span> Mammalian protein found in humans

Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity, and iron export. It is coded for by the gene APP and regulated by substrate presentation. APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.

<span class="mw-page-title-main">Neurodegenerative disease</span> Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

Christine Van Broeckhoven is a Belgian molecular biologist and professor in Molecular genetics at the University of Antwerp. She is also leading the VIB Department of Molecular Genetics, University of Antwerp of the Flanders Institute for Biotechnology (VIB). Christine Van Broeckhoven does research on Alzheimer dementia, bipolar mental disorders and other neurological diseases. Since 1983 she has had her own laboratory for molecular genetics at the University of Antwerp, and since 2005 is focussing her research on neurodegenerative brain diseases. She is an associate editor of the scientific journal Genes, Brain and Behavior.

Sir John Anthony Hardy is a human geneticist and molecular biologist at the Reta Lila Weston Institute of Neurological Studies at University College London with research interests in neurological diseases.

<span class="mw-page-title-main">SORL1</span> Protein-coding gene in the species Homo sapiens

Sortilin-related receptor, L(DLR class) A repeats containing is a protein that in humans is encoded by the SORL1 gene.

<span class="mw-page-title-main">Roskamp Institute</span>

The Roskamp Institute, was co-founded by Robert and Diane Roskamp, and Fiona Crawford and Michael Mullan in Sarasota, Florida in 2003. It is a nonprofit biomedical research facility specializing neurological research including Alzheimer's disease, traumatic brain injury, Gulf War syndrome, and posttraumatic stress disorder. It also operates an onsite neurology clinic. The institute is focused on finding the causes and treatments for neuropsychiatric and neurodegenerative diseases.

Bart De Strooper is a Belgian molecular biologist and professor at Vlaams Instituut voor Biotechnologie and KU Leuven and the UK Dementia Research Institute and University College London, UK. De Strooper's research seeks to translate genetic data into the identification and treatment of neurodegenerative diseases and treatments. interest are the secretases, proteases which cleave the amyloid precursor protein (APP), resulting in amyloid peptides.

Early-onset Alzheimer's disease (EOAD), also called younger-onset Alzheimer's disease (YOAD), is Alzheimer's disease diagnosed before the age of 65. It is an uncommon form of Alzheimer's, accounting for only 5–10% of all Alzheimer's cases. About 60% have a positive family history of Alzheimer's and 13% of them are inherited in an autosomal dominant manner. Most cases of early-onset Alzheimer's share the same traits as the "late-onset" form and are not caused by known genetic mutations. Little is understood about how it starts.

Genetic heterogeneity occurs through the production of single or similar phenotypes through different genetic mechanisms. There are two types of genetic heterogeneity: allelic heterogeneity, which occurs when a similar phenotype is produced by different alleles within the same gene; and locus heterogeneity, which occurs when a similar phenotype is produced by mutations at different loci.

The Swedish mutation, or familial Alzheimer's disease genetic mutation, is one of the most well known genetic variations that causes early-onset familial Alzheimer's disease.

<span class="mw-page-title-main">Rudolph E. Tanzi</span> American geneticist

Rudolph Emile 'Rudy' Tanzi a professor of Neurology at Harvard University, vice-chair of neurology, director of the Genetics and Aging Research Unit, and co-director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital (MGH).

Joseph D. Buxbaum is an American molecular and cellular neuroscientist, autism researcher, and the Director of the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai. Buxbaum is also, along with Simon Baron-Cohen, the co-editor of the BioMed Central journal Molecular Autism, and is a member of the scientific advisory board of the Autism Science Foundation. Buxbaum is a Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences. He is also the Vice Chair for Research and for Mentoring in the Department of Psychiatry at the Icahn School of Medicine at Mount Sinai.

Robert Williamson is a retired British-Australian molecular biologist who specialised in the mapping, gene identification, and diagnosis of human genetic disorders.

Colin Louis MastersMD is an Australian neuropathologist who researches Alzheimer's disease and other neurodegenerative disorders. He is laureate professor of pathology at the University of Melbourne.

Alison Mary Goate is a professor of neuroscience and Director of the Loeb Center for Alzheimer's Disease at Icahn School of Medicine at Mount Sinai, New York City. She was previously professor of genetics in psychiatry, professor of genetics, and professor of neurology at Washington University School of Medicine.

Rosa Rademakers is an American neurogeneticist and professor within the Department of Neuroscience at the Mayo Clinic. Her research centers on the genetic basis of neurodegenerative diseases, such as identifying causal genes and their function, exploring familial risk factors, and the mechanism of the degeneration. Her neurodegenerative diseases of focus include "Alzheimer's disease (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)." She received a Bachelor of Arts in Biology, a Master of Arts in Biochemistry, and a Ph.D. in Science, all from the University of Antwerp. Originally from the Netherlands, she came to the Mayo Clinic in 2005 for a post-doctoral fellowship, and in 2007 she was given a lab director position.

<span class="mw-page-title-main">Martin Rossor</span>

Martin Neil Rossor, is a British clinical neurologist with a specialty interest in degenerative dementias and familial disease.

Dennis J. Selkoe is an American physician (neurologist) known for his research into the molecular basis of Alzheimer's disease. In 1985 he became Co-Director of the Center for Neurological Diseases and from 1990, Vincent and Stella Coates Professor of Neurological Diseases at Harvard Medical School. He is also a Fellow of the AAAS and a member of the National Academy of Medicine.

<span class="mw-page-title-main">Carol Jennings</span> British Alzheimers advocate and campaigner

Carol Joyce Jennings is a British campaigner and advocate for research into Alzheimer's Disease. As of 2023 she serves as an honorary Vice-President of the Alzheimer's Society. Through her activism in the 1980s, Jennings brought her family to the attention of researchers studying the disease, which subsequently led to the discovery of the London Mutation. This mutation, found on the Amyloid Precursor Protein (APP) gene located on chromosome 21, marked a significant breakthrough in understanding the genetic basis of Alzheimer's Disease and provided evidence for the development of the 'amyloid hypothesis', which attempts to explain the underlying causes of Alzheimer's Disease.

References

  1. ↑ "Alzheimer's Disease Research: Scientific Productivity and Impact of the Top 100 Investigators in the Field".
  2. ↑ US 5877015,John Anthony Hardy, Marie-Christine Chartier-Harlin, Alison Mary Goate, Michael John Owen, Michael John Mullan,"APP770 mutant in alzheimer's disease",published 1999-03-02
  3. ↑ US 5795963,Michael John Mullan,"Amyloid precursor protein in alzheimer's disease",published 1998-08-18
  4. ↑ Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L (1991). "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease". Nature. 349 (6311): 704–706. Bibcode:1991Natur.349..704G. doi:10.1038/349704a0. PMID   1671712. S2CID   4336069.
  5. 1 2 Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, Goate A, Rossor M, Roques P, Hardy J, Mullan M (1991). "Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene". Nature. 353 (6347): 844–846. Bibcode:1991Natur.353..844C. doi:10.1038/353844a0. PMID   1944558. S2CID   4345311.
  6. 1 2 3 Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, Lannfelt L (1992). "A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N−terminus of Beta-Amyloid". Nature Genetics. 1 (5): 345–347. doi:10.1038/ng0892-345. PMID   1302033. S2CID   20046036.
  7. ↑ "About the Roskamp Institute". Roskamp Institute. 29 December 2015. Retrieved July 3, 2017.
  8. ↑ "Our Leadership". Rock Creek Pharmaceuticals. Retrieved June 6, 2016.
  9. ↑ "Management & Scientific Team". Archer Pharmaceuticals. Retrieved June 6, 2016.
  10. ↑ "'Unstoppable Passion' | Business Observer". 5 March 2009.
  11. ↑ "The History of the Roskamp Institute". 28 December 2015.
  12. 1 2 "Sarasota scientists excited about potential Alzheimer's breakthrough - HT Health". health.heraldtribune.com. Retrieved 27 June 2023.
  13. ↑ "Sarasota's Roskamp Institute developing groundbreaking Alzheimer's drug | MySuncoast Health | mysuncoast.com". Archived from the original on 2016-10-05. Retrieved 2016-10-03.
  14. ↑ "Roskamp Institute scientists searching for Alzheimer's breakthrough | Local News | mysuncoast.com". Archived from the original on 2016-10-05. Retrieved 2016-10-03.
  15. ↑ "Roskamp Institute research could help veterans - HT Health". health.heraldtribune.com. Retrieved 27 June 2023.
  16. ↑ "Roskamp Institute - Sarasota, Florida". www.clinicaltrialsgps.com. Retrieved 27 June 2023.
  17. ↑ "Using a mouse model of Gulf War Illness, researchers dig deep for potential treatments".
  18. ↑ "Memorandum" (PDF). justia.com. Retrieved 27 June 2023.
  19. ↑ UK Patents Act, 1977, c.37
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