Help with difficult diagnoses (2009)

Maurice Wilkins Centre scientists have developed a new way of classifying patients with rare forms of amyloidosis – a potentially fatal disease where protein deposits called amyloids accumulate in various tissues. 

Under the direction of Professor Garth Cooper (centre), Dr Mia Jüllig and Mr Martin Middleditch have identified the proteins in some unusual amyloid samples using the Centre’s advanced mass spectrometer. 

Professors Peter Browett and Kathy Crosier, both clinicians at Auckland Hospital, approached Professor Cooper about examining unusual amyloid samples after conventional laboratory studies failed to determine the type of amyloid protein in their patients. 

Professor Cooper took up this challenge with his team, armed with more than 30 years of clinical interest in amyloidoses and a strong track record in cutting-edge techniques to identify novel proteins. 

“Amyloids are typically made up of a single main protein called an ‘amyloid monomer’, and a number of minor matrix proteins. The identity of the monomer yields key information that supports both diagnosis and specific therapeutic options,” explains Professor Cooper. 

“There can be dozens of other proteins in an amyloid,” says Dr Jüllig, a Maurice Wilkins Centre research fellow. “Some of these proteins provide further clues as to how the amyloid developed.” 

Most pathologists identify which proteins are in amyloid samples by probing them with antibodies. However, this technique is not always accurate and is limited to known proteins, so it’s hard to identify new types of amyloid proteins in unusual patients. 

The Maurice Wilkins Centre team took a high-tech approach to three patient samples that couldn’t be classified with existing techniques. 

“Amyloids are clumps of insoluble protein,” says Mr Middleditch. “Our technique relies on performing the difficult task of converting these proteins into a soluble form so that they can be processed and identified in our mass spectrometer. We can then get a very good picture of what proteins are in the diseased tissue.” 

The three amyloid samples, from the heart, liver, and radial nerve (in the arm) have all produced clear, unambiguous results. 

“We’d like to use this technology to help as many patients as possible, both nationally and internationally,” says Mr Middleditch.