New PET scan tracer allows first imaging of the epigenetics of the human brain

A novel PET radiotracer developed at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH) is able for the first time to reveal epigenetic activity – the process that determines whether or not genes are expressed – within the human brain. In their report published in Science Translational Medicine, a team of MGH/Martinos Center investigators reports how their radiochemical – called Martinostat – shows the expression levels of important epigenetics-regulating enzymes in the brains of healthy volunteers.

“The ability to image the epigenetic machinery in the human brain can provide a way to begin understanding interactions between genes and the environment,” says Jacob Hooker, PhD, of the Martinos Center, senior author of the report. “This could allow us to investigate questions such as why some people genetically predisposed to a disease are protected from it? Why events during early life and adolescence have such a lasting impact on brain health? Is it possible to ‘reset’ gene expression in the human brain?”

A key epigenetic mechanism is the packaging of DNA into chromosomes, in which it wraps around proteins called histones forming a structure called chromatin. Modification of histones by the addition or removal of molecules called epigenetic factors can regulate whether or not an adjacent gene is expressed. One of the most important of these factors is the acetyl molecule, addition of which allows a gene to be transcribed and removal of which – called deacetylation – prevents transcription.



Enzymes called histone deacetylases (HDAC) are important regulators of gene transcription, and one group of HDACs has been linked to important brain disorders. Several established neuropsychiatric drugs are HDAC inhibitors, and others are currently being studied as potential treatment for Alzheimer’s disease and Huntington’s disease. Martinostat was developed in Hooker’s laboratory and is patterned after known HDAC inhibitors in order to tightly bind to HDAC molecules in the brain.

PET scans with Martinostat of the brains of eight healthy human volunteers revealed characteristic patterns of uptake – reflecting HDAC expression levels – that were consistent among all participants. HDAC expression was almost twice as high in gray matter as in white matter; and within gray matter structures, uptake was highest in the hippocampus and amygdala and lowest in the putamen and cerebellum. Experiments with brain tissues from humans and baboons confirmed Martinostat’s binding to HDAC, and studies with neural progenitor stem cells revealed specific genes regulated by this group of HDACs, many of which are known to be important in brain health and disease.

“HDAC dysregulation has been implicated in a growing number of brain diseases, so being able to study HDAC regulation both in the normal brain and through the progression of disease should help us better understand disease processes,” says Hooker, who is an associate professor of Radiology at Harvard Medical School. “We’ve now started studies of patients with several neurologic or psychiatric disorders, and I believe Martinostat will help us understand the different ways these conditions are manifested and provide new insights into potential therapies.”

More information can be found from Massachusetts General Hospital website.

Chinesse medical device manufacturers to compete globally

HUAWEI is now absolutely a globally recognized brand name, and definitely a rising star in its cluster. Perhaps within 3-5 years, there will be a new 'LENOVO' or a new 'HUAWEI' in medical device industry as well.

Currently there are around 150.000 medical device manufacturers in China, but 90% of them can only achieve a yearly turnover between RMB 10-20 million. Most of them are producing medical disposables or small devices like thermometer, blood glucose meter, blood pressure monitor, or ECG monitor, many are on OEM basis.

In Chinese hospitals, for equipment like MRI, CT or endoscopy, some 90% are imported products. But the situation starts to change now, slowly. Since2013, we see Chinese manufacturers are releasing new products including ultra-sound scanner, MRI, CT and even PET-CT, as well as bio-chemical analyzer and etc, all under manufacturers' own R&D with self-owned intellectual property rights.

So far these Made in China products can't compete effectively in international market with those global leaders, but a long march to the global med tech market with Chinese domestic market as a starting point is logical and realistic. As long as the Chinese medical device manufacturers accumulate knowledge and experience in product and market development, strengthen the capability in research and innovation and with practical strategy and patience, they will obtain a decent market share not only in Chinese domestic market, but also in international medica device market.

How to find distributors in China Market

Basically the nature of the very medical device a manufacturer is about to market in China (please check our other article on 'things to consider before entering China market') will be the key factor to be considered in marketing strategy. China is large in territory, and sometimes the situation may vary from province to province. One recommendable strategy is to divide the entire market into several sub-markets, then find different distributors to cover each individual sub-market.

Since the purchase of medical equipment by a hospital must go through public bidding, a strong local player may be a good partner of a device producer. Nowadays it's getting more and more difficult for a distributor to cover the entire national market, therefore a good set up of sub-markets and well selected regional distributors will assist medical device manufacturers to achieve a quick win in China market.

Hospitals in the eastern provinces are the consumers of high end medical devices/equipment, no matter it is a PET-CT or a surgery robot, or RFID tracking system for OR. One may find the same type of clients in some inland cities, where there are renown hospitals (mostly affiliated to a medical university) or top experts in a certain academic sector.

While hospitals in inland provinces must try the best to balance between demand and budget, stents and crafts definitely have market there, or MRI, but not likely for PET-CT kind of things. Anyhow, the vast territory of mid-west of China is an ideal stage for most of the devices, from Class I to Class III, provided you have the right product for the right client, with the help from the right partner.

For an imaging device manufacturer, a distributor with good back ground in the same sector could be ideal, but sometimes it is not necessarily the case. One of the important criterion is the capability to penetrate. If the distributor has good connections in his territory and is good at securing business, imaging or lab background shall not rank Nr. 1 when per-qualifying a distributor.

In China, NOT all the companies can market medical devices. Only those licensed business entities can legally sell medical devices/equipment, including imported medical devices (please check our other article on 'how to register medical devices to China SFDA').