Leading expert in multiple sclerosis and neuromyelitis optica, Dr. Paul Matthews, MD, explains major breakthroughs in personalized medicine for MS. He details how genetic research confirmed MS as a primary autoimmune disease. Dr. Matthews describes the discovery of the aquaporin-4 antibody, which distinguishes neuromyelitis optica from MS. He highlights how precision medicine enabled the safe reintroduction of natalizumab (Tysabri) by managing PML risk. These advances allow for more accurate diagnosis and tailored treatment decisions.
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Advances in Personalized Medicine for Multiple Sclerosis Diagnosis and Treatment
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- Genetic Breakthroughs in MS
- Aquaporin-4 Antibody Discovery
- Neuromyelitis Optica Spectrum
- Precision Medicine and Tysabri
- Managing PML Risk
- Future of MS Treatments
- Full Transcript
Genetic Breakthroughs in MS
Dr. Paul Matthews, MD, identifies genetics as a third major breakthrough area in multiple sclerosis. Large genome-wide association studies began in the late 2000s. An international consortium of scientists collaborated on this revolutionary work.
This research had two profound implications. First, it highlighted the predominance of inflammatory genes as susceptibility factors. This genetic evidence strongly supports the view that MS is a primary autoimmune disease.
Aquaporin-4 Antibody Discovery
The discovery of the aquaporin-4 antibody represents another critical advance. This antibody has a close relationship with neuromyelitis optica (NMO). Dr. Paul Matthews, MD, explains this finding allowed NMO to be defined as a distinct disease entity separate from traditional multiple sclerosis.
This distinction is crucial for patient care. Accurate identification enables correct treatment selection from diagnosis. Patients with NMO do not respond well to conventional MS therapies and may even worsen on them.
Neuromyelitis Optica Spectrum
The understanding of neuromyelitis optica has expanded significantly. Dr. Paul Matthews, MD, notes that the spectrum of NMO is much broader than previously recognized. This expanded definition helps clinicians identify more patients who might have been misdiagnosed with MS.
Proper diagnosis is essential because treatment approaches differ substantially between NMO and MS. This precision in diagnosis directly improves patient outcomes by ensuring appropriate therapy.
Precision Medicine and Tysabri
Precision medicine rescued the use of natalizumab (Tysabri) for multiple sclerosis treatment. Dr. Anton Titov, MD, discusses this development with Dr. Matthews. The medication faced a terminal threat to its regulatory approval after being associated with progressive multifocal leukoencephalopathy (PML).
This serious brain infection initially jeopardized the drug's future. However, precision medicine approaches provided a solution. Researchers developed methods to identify which patients were at risk for developing PML.
Managing PML Risk
Dr. Paul Matthews, MD, explains how clinicians now manage PML risk with natalizumab. Patients can be monitored closely over time to serially evaluate their PML risk. This ongoing assessment allows for rational decision-making between patients and doctors.
These decisions include whether to use Tysabri and for how long to continue treatment. This risk management strategy has made natalizumab available again as an effective MS medication while prioritizing patient safety.
Future of MS Treatments
The collaborative model of the genetics consortium has profound implications beyond multiple sclerosis. Dr. Paul Matthews, MD, emphasizes how scientists worldwide worked together with common purpose. They joined data and made results freely available to the medical community.
This approach enabled the assembly of large data volumes necessary for breakthroughs. Dr. Anton Titov, MD, and Dr. Matthews agree this model will continue driving advances in personalized medicine for neurological conditions.
Full Transcript
Dr. Anton Titov, MD: You published a review of multiple sclerosis advances in diagnosis and treatment. It was printed in the leading journal Nature Reviews Neurology. Your review is titled "Decade in review: multiple sclerosis. New multiple sclerosis medications. Personalized medicine for multiple sclerosis." What are leading breakthroughs in personalized medicine for multiple sclerosis treatment?
Dr. Paul Matthews, MD: The third area of breakthroughs in multiple sclerosis is in the genetics of multiple sclerosis. We talked about this earlier in the interview. This work began in the latter part of the first decade of this century.
There was the first of the large genome-wide association clinical trials in multiple sclerosis. Results began to be published from the international consortium. This was a revolutionary development for two reasons.
First, it clearly highlighted that predominance of inflammatory genes as susceptibility factors for multiple sclerosis. It clearly emphasizes to my mind that multiple sclerosis is a primary autoimmune disease.
The second aspect of this work has very profound implications for multiple sclerosis diagnosis and treatment. It has also significance for medicine more widely. The genetics consortium represented a grouping of scientists from all over the globe.
All multiple sclerosis experts worked together with common purpose. They joined their data together. They made multiple sclerosis research results freely available for development by the medical community. That allowed the large volumes of data to be assembled. We needed that.
Breakthrough #4 was the discovery of the aquaporin 4 antibody and its close relationship with neuromyelitis optica [NMO]. It allowed NMO to be defined as a distinct disease entity. Neuromyelitis optica is different from traditional multiple sclerosis.
This has enabled patients with NMO to be carefully identified from diagnosis. It allowed the correct treatment to be delivered. Because these patients don't respond to multiple sclerosis treatments well. They may even show worsening with conventional multiple sclerosis therapies.
Moreover, the spectrum of NMO [neuromyelitis optica] has been broadly expanded. We recognize that NMO involves much more than we thought before.
Dr. Anton Titov, MD: We have talked about personalized medicine. It has been exciting to see precision medicine in multiple sclerosis. Precision medicine rescued the use of Natalizumab (Tysabri) after the recognition of its association with progressive neurological disease. It is Progressive Multifocal Leukoencephalopathy infection, PML.
Initially the identification of Progressive Multifocal Leukoencephalopathy posed a terminal threat to regulatory approvals of this multiple sclerosis medication. However, we discovered methods of identifying patients at risk for PML.
Dr. Paul Matthews, MD: We can monitor patients closely over time to serially evaluate this risk of Progressive Multifocal Leukoencephalopathy. Therefore, natalizumab is used again to treat multiple sclerosis.
Dr. Anton Titov, MD: Rational decisions can be made between a patient and a doctor about whether natalizumab should be used and for how long. Tysabri is an effective multiple sclerosis medication.