Cell Guidance Systems Blog

Just a decade ago, for the millions of people living with rare genetic diseases, there seemed little hope that an effective treatment could be developed. One of the main obstacles is the massive costs of drug development; for many rare genetic diseases, there aren't even enough patients to conduct a formal clinical trial. But changes to the regulatory framework and the development of gene therapy platform technologies that, once proven safe, may be rapidly turned to a wide number of disparate diseases, is offering hope.

The use of extracellular vesicles for regenerative and therapeutic applications is gaining currency. Notably, exosomes derived from mesenchymal stem cells (MSCs), have garnered attention. However, even manufacturing exosomes for relatively small-scale, preclinical and clinical activity has proved challenging. How will scalable production of vast quantities of exosomes for routine therapeutic use be achieved?

Immunomodulatory drugs, such as Immune-checkpoint inhibitors (ICIs) have transformed cancer care. However, as with other cancer drugs, ICIs are associated with significant adverse events which can even be fatal. How do these occur and what is being done to reduce their severity?

Since the 1986 approval of Muromonab, the first therapeutic monoclonal antibody (mAb), used to treat steroid-resistant transplant patients, mAbs have rapidly evolved and gained clinical ground become the largest class of biopharmaceuticals. During this period, mAbs have garnered a reputation for safety, favourable PKPD, and high levels of specificity that have made them a preferred drug modality in many therapeutic applications.

Antimicrobial resistance (AMR) is on the rise. By 2050, AMR may be killing more people than cancer does now. Already, the mortality rates and economic impact are alarming. According to the Centre for Disease Control the total cost of AMR in the USA is estimated at $55bn and results in over 35,000 deaths each year. The worldwide death toll is ticking over 700,000.

Little more than 10 years ago, the prospects for gene therapy were bleak. Early clinical trials had served to highlight the risks. In particular, the 1999 death of Jesse Gelsinger proved a turning point, and clinical progress stalled for years. The risks are now better understood and controlled, and in recent years so much has changed. The FDA's 2017 approval of the first human gene therapy drug, Luxurna, heralded a new era with a further twenty gene therapies approved by 2019 with 1000 more in clinical trials.

16 years on from the groundbreaking development of induced Pluripotent Stem Cells (iPSCs), the scientific community has generated an explosion of applications in the areas of high throughput drug discovery and developmental biology research. Personalised regenerative medicine and cell-based therapies are also on the horizon. But after all these years, iPSC-based therapy remains in its infancy. What are the future prospects?

Blood is a complex, dynamic mixture of cells, proteins, ions, sugars, hormones, nutrients, gases and more. The composition of blood constantly varies in response to our diet, exercise status, hydration, time of the day, injury and challenges from pathogens. As well as its role in mammals, blood products such as serum and albumin are important reagents for cell culture. What are the components of blood? Where do these components of blood come from?

For a drug to be successful, just as important as what the drug does to the body, is what the body does to the drug. Not only is it important to transport therapeutic drugs effectively to where they are needed, but once it is there, they have to remain long enough to have an effect. Studies to understand a drug's journey through the body are in the domain of drug metabolism and pharmacokinetics, usually abbreviated to DMPK.

From 1957 to 1961, Thalidomide, a small molecule drug, was prescribed to treat a range of conditions in pregnant women including morning sickness. The developmental abnormalities that it caused in the developing foetus made the drug synonymous with pharmaceutical negligence. Despite this, in 1988, thalidomide was approved for the safe treatment of leprosy and cancer.