Tomorrow's Health, Today's Research

Dr. Patrick MacLeod

Adjunct Professor, Biology Department
Clinical Geneticist and Pediatrician, Vancouver Island Health Authority
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Phone: (250) 727-4461
Research area: genetic mechanisms of inherited diseases

Research Profile:

Vital link to patients

As a medical doctor and clinical investigator, Dr. Patrick MacLeod is a vital link between molecular researchers at the Centre for Biomedical Research and patients in Greater Victoria.

He recently stepped down as medical director of the Medical Genetics Program at the Victoria General Hospital. He now divides his time between teaching in UVic's Biology Department, clinical work with the Vancouver Island Health Authority and collaborating on numerous research projects.

MacLeod’s specialty is tracking and diagnosing genetic disorders. He is currently excited by two projects: finding a genetic cure for Rett syndrome, and developing prenatal screening for Spinal Cerebular Ataxia type 2 (SCA2) with collaborators in Cuba.

Rett syndrome: from diagnosis to cure

Rett syndrome is one of the most common types of genetic diseases in Canada with one in 10,000 girls affected. It is a neurological disorder that occurs exclusively in girls. Babies with Rett syndrome appear to develop normally until six to 18 months of age. They then enter a period of regression, losing speech and motor skills. Most of the children develop seizures, repetitive hand movements, developmental delay and motor-control problems.

The disorder has attracted a lot of attention from geneticists because it is one of the most promising candidates for gene therapy. Several scientists from the CBR are working on Rett syndrome from different angles including Dr. Juan Ausio and Dr. Kerry Delaney.

MacLeod became interested in Rett syndrome when he joined the CBR in 1992. With his PhD student, Giovana de Amorim, and collaborators at the University of Montreal, he identified over 300 mutations (all in the same gene) that cause the disease. The group used this knowledge to develop a diagnostic screen, now used in Canada. Before the genetic test, it was difficult to distinguish Rett syndrome from other conditions that share many of the same symptoms.

However, MacLeod wants to move beyond just diagnosing the disease to curing it through gene therapy. He is collaborating with Delaney, his former student de Amorim and Dr. David Levin, a former CBR member, who is now at the University of Manitoba.

One challenge of gene therapy is figuring out how to deliver the gene to the area of the body where it is needed. This is especially true in Rett Syndrome, as the gene product is required in the brain. Any gene delivery system would have to cross the blood brain barrier.

MacLeod and his collaborators are working on a viral vector to carry the gene into the brain of mice that have Rett syndrome.

For safety reasons, it is unlikely that the final treatment for girls would involve a virus. However, the mice experiment will tell the researchers whether or not the therapy works once the gene makes it to the brain. MacLeod just began working on the next step: an intravenous delivery system which MacLeod feels will be more appropriate for humans.

New fetal testing for hereditary ataxia

Dr. Patrick MacLeod is an expert in tracking and diagnosing founder mutations. Founder mutations are those that have originated fairly recently within a single individual and have spread through an isolated community, often those on islands.

One example is a mutation that originated in Cuba that causes Spinocerebellar ataxia type 2 (SCA2).

SCA2 is a degenerative neurological disease that affects the cerebellum, the coordination center of the brain. It belongs to a group of diseases called ataxias that are characterized by incoordination and trouble with balance. SCA2 shows up in adult men and leads to trouble swallowing and death. It hits about 40 per 100,000 people in Cuba.

MacLeod has teamed up with the Centre for the Research and Rehabilitation of Hereditary Ataxia in Cuba and the Latin America Research Group in Victoria to work on a new prenatal screening technique.

Currently, prenatal screening involves chorionic villus sampling at 11 weeks of pregnancy. However, this method uses tissue culture techniques that are hard to afford in developing countries.

MacLeod and his collaborators are working on a test that purifies fetus DNA directly from amniotic fluid at 15 weeks. The collaborators are currently testing the diagnostic procedure in Cuba.